1zk2: Difference between revisions

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[[Image:1zk2.gif|left|200px]]
{{Seed}}
[[Image:1zk2.png|left|200px]]


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{{STRUCTURE_1zk2|  PDB=1zk2  |  SCENE=  }}  
{{STRUCTURE_1zk2|  PDB=1zk2  |  SCENE=  }}  


'''Orthorhombic crystal structure of the apo-form of R-specific alcohol dehydrogenase (mutant G37D) from Lactobacillus brevis'''
===Orthorhombic crystal structure of the apo-form of R-specific alcohol dehydrogenase (mutant G37D) from Lactobacillus brevis===




==Overview==
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The R-specific alcohol dehydrogenase (RADH) from Lactobacillus brevis is an NADP-dependent, homotetrameric member of the extended enzyme family of short-chain dehydrogenases/reductases (SDR) with a high biotechnological application potential. Its preferred in vitro substrates are prochiral ketones like acetophenone with almost invariably a small methyl group as one substituent and a bulky (often aromatic) moiety as the other. On the basis of an atomic-resolution structure of wild-type RADH in complex with NADP and acetophenone, we designed the mutant RADH-G37D, which should possess an improved cosubstrate specificity profile for biotechnological purposes, namely, a preference for NAD rather than NADP. Comparative kinetic measurements with wild-type and mutant RADH showed that this aim was achieved. To characterize the successful mutant structurally, we determined several, partly atomic-resolution, crystal structures of RADH-G37D both as an apo-enzyme and as ternary complex with NAD or NADH and phenylethanol. The increased affinity of RADH-G37D for NAD(H) depends on an interaction between the adenosine ribose moiety of NAD and the inserted aspartate side-chain. A structural comparison between RADH-G37D as apo-enzyme and as a part of a ternary complex revealed significant rearrangements of Ser141, Glu144, Tyr189 and Met205 in the vicinity of the active site. This plasticity contributes to generate a small hydrophobic pocket for the methyl group typical for RADH substrates, and a hydrophobic coat for the second, more variable and often aromatic, substituent. Around Ser141 we even found alternative conformations in the backbone. A structural adaptability in this region, which we describe here for the first time for an SDR enzyme, is probably functionally important, because it concerns Ser142, a member of the highly conserved catalytic tetrad typical for SDR enzymes. Moreover, it affects an extended proton relay system that has been identified recently as a critical element for the catalytic mechanism in SDR enzymes.
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==About this Structure==
==About this Structure==
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==Reference==
==Reference==
Atomic resolution structures of R-specific alcohol dehydrogenase from Lactobacillus brevis provide the structural bases of its substrate and cosubstrate specificity., Schlieben NH, Niefind K, Muller J, Riebel B, Hummel W, Schomburg D, J Mol Biol. 2005 Jun 17;349(4):801-13. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15896805 15896805]
Atomic resolution structures of R-specific alcohol dehydrogenase from Lactobacillus brevis provide the structural bases of its substrate and cosubstrate specificity., Schlieben NH, Niefind K, Muller J, Riebel B, Hummel W, Schomburg D, J Mol Biol. 2005 Jun 17;349(4):801-13. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15896805 15896805]
The crystal structure of R-specific alcohol dehydrogenase from Lactobacillus brevis suggests the structural basis of its metal dependency., Niefind K, Muller J, Riebel B, Hummel W, Schomburg D, J Mol Biol. 2003 Mar 21;327(2):317-28. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12628239 12628239]
Morphological study of allogeneic tumor growth in mice bearing a glass cylinder., Filippa DA, Dosne Pasqualini C, Medicina (B Aires). 1975 Jan-Feb;35(1):29-36. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/1092950 1092950]
[[Category: Lactobacillus brevis]]
[[Category: Lactobacillus brevis]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: R-specific alcohol dehydrogenase]]
[[Category: R-specific alcohol dehydrogenase]]
[[Category: Short chain reductases/dehydrogenase]]
[[Category: Short chain reductases/dehydrogenase]]
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